Colchicine for Chronic Kidney Disease

Recruiting in Palo Alto (17 mi)

Overseen by Leo F Buckley, PharmD MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Brigham and Women's Hospital

Must be taking: ACE inhibitors, SGLT2 inhibitors

Must not be taking: Immunosuppressives, Antimicrobials, P-gp inhibitors, CYP3A4 inhibitors

Disqualifiers: Heart failure, Kidney failure, Malignancy, others

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This study is designed to determine the efficacy and safety of colchicine in patients with chronic kidney disease.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as immunosuppressive or anti-inflammatory drugs, systemic antimicrobial therapy, and medications that may cause muscle problems. If you are taking any of these, you may need to stop them at least 30 days before joining the study.

Is colchicine safe for humans?

There is no specific safety data on colchicine for chronic kidney disease in the provided research articles. ^{1 2 3 4 5}

How does the drug colchicine differ from other treatments for chronic kidney disease?

Colchicine is unique because it is traditionally used to treat gout and inflammation, and its use in chronic kidney disease (CKD) is novel, as there are currently no drugs that can halt the progression of kidney damage in CKD. This makes colchicine a potentially new option for managing CKD, focusing on its anti-inflammatory properties. ^{6 7 8 9 10}

Research Team

Leo F Buckley, PharmD MPH

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

Adults aged 21-80 with chronic kidney disease, inflammation (high C-reactive protein levels), and heart strain are eligible. They must be able to consent, follow the study plan, have an eGFR of 15-75 mL/min/1.73 m2, and a high urine albumin level. Exclusions include colchicine allergy, recent hospitalization or surgery, severe heart failure or other serious conditions that increase risk.

Inclusion Criteria

My doctor thinks I should take a medication for sugar control in my blood.

Your heart function was very weak in the past year.

My kidney function, measured by eGFR, is between 15 to 75 mL/min.

Exclusion Criteria

I have a heart condition I was born with.

You have a serious illness or condition that makes the doctor think participating in the study could be risky for you.

I have had surgery in the last 30 days or will have it during the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive colchicine or placebo once daily to assess efficacy and safety

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Colchicine (Anti-inflammatory)

Trial Overview The trial is testing if colchicine can safely reduce inflammation in patients with chronic kidney disease compared to a placebo. Participants will either receive colchicine or a placebo pill without knowing which one they're getting to measure the true effect of the drug.

Participant Groups

Group I: Colchicine Experimental Treatment 1 Intervention

Colchicine 0.3 mg once daily

Group II: Placebo Placebo Group 1 Intervention

Placebo once daily

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Dr. William Curry

Brigham and Women's Hospital

Chief Medical Officer

MD from Columbia University College of Physicians and Surgeons

Dr. Scott Schissel

Brigham and Women's Hospital

Chief Executive Officer since 2021

MD from Columbia University College of Physicians and Surgeons

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

A 39-year-old man on hemodialysis for chronic renal failure developed skin lesions consistent with porphyria cutanea tarda (PCT), with significantly elevated plasma porphyrins, particularly uroporphyrin, indicating a potential link between hemodialysis and PCT.

The study suggests that the increase in plasma porphyrins in patients undergoing hemodialysis may not be solely due to inadequate clearance, but could involve factors affecting the enzyme uroporphyrinogen decarboxylase, highlighting a possible mechanism of action in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Porphyria cutanea tarda in a chronic hemodialysis patient]. Kano, T., Yamane, Y., Suzuki, M., et al.[2011]

A nationwide study of 10,805 patients with advanced chronic kidney disease found that UVB phototherapy did not increase the risk of developing skin cancer compared to those who did not receive UVB treatment, even after a median follow-up of 75 months.

Patients receiving more UVB phototherapy also showed no increased risk of skin cancer, suggesting that UVB treatment is a safe option for managing uraemic pruritus in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Skin Cancer among Patients with Chronic Kidney Disease Treated with Ultraviolet B Phototherapy for Uraemic Pruritus: A Nationwide Cohort Study. Ko, MJ., Huang, JW., Wu, HY., et al.[2022]

In two female patients undergoing prolonged maintenance hemodialysis, the development of blisters and postbullous erosions was observed, indicating potential skin complications associated with this treatment.

One patient exhibited elevated levels of uroporphyrin I and III in the urine, suggesting a possible link between hemodialysis and porphyrin metabolism disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Porphyria cutanea tarda-like aspects in two prolonged hemodialysis patients (author's transl)]. Korting, GW.[2006]

The patient exhibited symptoms consistent with hereditary coproporphyria, including elevated levels of specific porphyrin metabolites, and a significant reduction in coproporphyrinogen oxidase activity, which is crucial for porphyrin metabolism.

Molecular analysis identified a novel mutation in the coproporphyrinogen oxidase gene, confirming the hereditary nature of the condition in the patient's family, as all affected relatives showed similar biochemical abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular, immunological, enzymatic and biochemical studies of coproporphyrinogen oxidase deficiency in a family with hereditary coproporphyria. Gross, U., Puy, H., Kühnel, A., et al.[2006]

A large study of over 1.5 million Taiwanese patients with chronic kidney disease (CKD) found that they have a 1.14-fold increased risk of developing non-melanoma skin cancer (NMSC) compared to the general population.

The risk is particularly high in pre-dialysis stage 5 CKD patients, especially those with anemia (1.48-fold increase) and those experiencing uraemic pruritus after long-term antihistamine treatment (1.38-fold increase).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Non-melanoma Skin Cancer in Patients with Chronic Kidney Disease and its Relationship to Uraemic Pruritus. Wang, CC., Tang, CH., Huang, SY., et al.[2022]

Chronic kidney disease (CKD) affects about 10% of the population, with diabetes being the most common cause, and it significantly increases the risk of cardiovascular events, dialysis dependency, and mortality as kidney function declines.

Current guidelines recommend that patients with a glomerular filtration rate (GFR) of ≤30 or ≤60 ml/min/1.73 m², especially with additional risk factors, should be referred to a nephrologist, highlighting the importance of early intervention in CKD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What is confirmed in the treatment of chronic kidney disease?] Greite, R., Schmidt-Ott, K.[2022]

Chronic kidney disease (CKD) is a significant health issue in Croatia, with high management costs for patients in end-stage CKD, highlighting the need for effective early detection and management strategies.

Currently, there is no drug to stop the progression of CKD, so the focus is on screening, specific therapies, and managing complications, emphasizing the importance of patient compliance and education for both healthcare providers and the public.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What do we know about chronic kidney disease at the beginning of the 21st century?]. Kes, P.[2018]

In a retrospective study involving 155 patients with chronic glomerulonephritis, therapies combining cytostatics, platelet aggregation inhibitors, and anticoagulants (CAA-therapy) showed favorable results, particularly in cases of nephrotic syndrome and glomerulonephritis with significant clinical symptoms.

Additional prednisone therapy (CAAP-therapy) also demonstrated effectiveness, while patients with clinically inactive nephritis and only urinary findings did not respond to these treatments, indicating that the therapy is most beneficial for active disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New results concerning the effectiveness of therapy of chronic glomerulonephritis. Results of cytostatics-anticoagulants-aggregation inhibitors, cystostatics-anticoagulants-aggregation inhibitors-prednisone and cystostatics-prednisone therapy, derived from a retrospective study]. Sinn, W., Ratner, M., Tomilina, N., et al.[2013]

A systematic review of glomerulonephritis management emphasizes the importance of tailored treatment based on histological type, with specific recommendations for conditions like IgA nephropathy, minimal change nephropathy, and membranous nephropathy, based on extensive literature analysis.

For minimal change nephropathy and focal segmental glomerulosclerosis, initial treatment in children typically involves prednisone, while adults may experience slower responses but fewer relapses, highlighting the need for age-specific treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Instructions and implementations for percutaneous renal biopsy. Guidelines for the therapy of glomerular nephropaties]. Cagnoli, L.[2017]

In a study of 98 hypertensive patients with chronic kidney disease (CKD), antihypertensive therapy significantly improved their estimated glomerular filtration rate (eGFR) from 51.87 to 57.55 mL/min/1.73 m² over 3 years (P<.001).

In contrast, eGFR decreased in patients without CKD, indicating that antihypertensive therapy specifically benefits those with CKD by preventing further decline in kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimated glomerular filtration rate reversal by blood pressure lowering in chronic kidney disease: Japan Multicenter Investigation for Cardiovascular DiseaseB CKD study. Yui, Y., Kodama, K., Hirayama, A., et al.[2021]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Porphyria cutanea tarda in a chronic hemodialysis patient]. [2011]

2. Sweden pubmed.ncbi.nlm.nih.gov

Risk of Skin Cancer among Patients with Chronic Kidney Disease Treated with Ultraviolet B Phototherapy for Uraemic Pruritus: A Nationwide Cohort Study. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

[Porphyria cutanea tarda-like aspects in two prolonged hemodialysis patients (author's transl)]. [2006]

4. France pubmed.ncbi.nlm.nih.gov

Molecular, immunological, enzymatic and biochemical studies of coproporphyrinogen oxidase deficiency in a family with hereditary coproporphyria. [2006]

5. Sweden pubmed.ncbi.nlm.nih.gov

Risk of Non-melanoma Skin Cancer in Patients with Chronic Kidney Disease and its Relationship to Uraemic Pruritus. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

[What is confirmed in the treatment of chronic kidney disease?] [2022]

7. Croatia pubmed.ncbi.nlm.nih.gov

[What do we know about chronic kidney disease at the beginning of the 21st century?]. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

[New results concerning the effectiveness of therapy of chronic glomerulonephritis. Results of cytostatics-anticoagulants-aggregation inhibitors, cystostatics-anticoagulants-aggregation inhibitors-prednisone and cystostatics-prednisone therapy, derived from a retrospective study]. [2013]

9. Italy pubmed.ncbi.nlm.nih.gov

[Instructions and implementations for percutaneous renal biopsy. Guidelines for the therapy of glomerular nephropaties]. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Estimated glomerular filtration rate reversal by blood pressure lowering in chronic kidney disease: Japan Multicenter Investigation for Cardiovascular DiseaseB CKD study. [2021]